tbuckley/cabot-search huggingface dataset:
Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1
Authors: Max M. Wattenberg, Heather Coho, Veronica M. Herrera, Kathleen Graham, Meredith L. Stone, Yuqing Xue, Renee B. Chang, Christopher Cassella, Mingen Liu, Shaanti Choi-Bose, Stacy K. Thomas, Hana Choi, Yan Li, Kelly Markowitz, Lauren Melendez, Michael Gianonne, Nandita Bose, Gregory L. Beatty
Journal: Science Immunology (2023)

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40. In mouse models of checkpoint inhibitor-resistant pancreatic cancer, coactivation of Dectin-1, via systemic β-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Antitumor activity was dependent on cDC1s and T cells but did not require classical T cell-mediated cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell-mediated IFN-γ signaling, which converged with Dectin-1 activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be invoked by coactivation of complementary myeloid signaling pathways.
Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool
Authors: Timm Weber, Sabrina Dähling, Svea Rose, Patrick Affeldt, Kanika Vanshylla, Leon Ullrich, Lutz Gieselmann, Finn Teipel, Henning Gruell, Veronica Di Cristanziano, Dae Sung Kim, George Georgiou, Manuel Koch, Christoph Kreer, Florian Klein
Journal: Science Immunology (2023)

The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond to repeated SARS-CoV-2 antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory B cell pool. We demonstrate that a subsequent breakthrough infection substantially increases the frequency of B cells encoding SARS-CoV-2-neutralizing antibodies. However, this is not primarily attributable to maturation, but to selection of preexisting B cell clones. Moreover, broadly reactive memory B cells arose early and even neutralized highly mutated variants like XBB.1.5 that the individuals had not encountered. Together, our data show that SARS-CoV-2 immunity is largely imprinted on Wu01 over the course of multiple antigen contacts but can respond to new variants through preexisting diversity.
Emergence and fate of stem cell–like <i>Tcf7</i> <sup>+</sup> CD8 <sup>+</sup> T cells during a primary immune response to viral infection
Authors: Joana Gomes Silva, Daniela Pais Ferreira, Alexandre Dumez, Tania Wyss, Romain Veber, Maxime Danilo, Daniel D. Pinschewer, Mélanie Charmoy, Werner Held
Journal: Science Immunology (2023)

In response to infection, naïve CD8+ T (TN) cells yield a large pool of short-lived terminal effector (TTE) cells that eliminate infected host cells. In parallel, a minor population of stem cell-like central memory (TCM) cells forms, which has the capacity to maintain immunity after pathogen clearance. It has remained uncertain whether stem-like TCM cells arise by dedifferentiation from a subset of cytolytic TTE cells or whether priming generates stem-like cells capable of seeding the TCM compartment and, if so, when cytolytic TTE cells branch off. Here, we show that CD8+ T cells with stem-like properties, which are identified by the expression of TCF1 (encoded by Tcf7), are present across the primary response to infection. Priming programs TN cells to undergo multiple cell divisions, over the course of which TCF1 expression is maintained. These TCF1+ cells further expand relatively independently of systemic inflammation, antigen dose, or affinity, and they quantitatively yield TCF1+ TCM cells after pathogen clearance. Inflammatory signals suppress TCF1 expression in early divided TCF1+ cells. TCF1 down-regulation is associated with the irreversible loss of self-renewal capacity and the silencing of stem/memory genes, which precedes the stable acquisition of a TTE state. TCF1 expression restrains cell cycling, explaining in part the limited expansion of TCF1+ relative to TCF1- cells during the primary response. Thus, our data are consistent with terminal differentiation of effector cells being a step-wise process that is initiated by inflammation in primed stem-like cells, which would otherwise become central memory cells by default.
Decoding atopic dermatitis: unveiling phenotypes through data-driven methods
Authors: Simone Cazzaniga, Dagmar Simon
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Decoding Atopic Dermatitis: Unveiling Phenotypes Through Data-Driven Methods Get access Simone Cazzaniga, Simone Cazzaniga Department of Dermatology, Inselspital University Hospital of Bern, Bern, SwitzerlandCentro Studi GISED, Bergamo, Italy Correspondence: Simone Cazzaniga, Email:simone.cazzaniga@gised.it https://orcid.org/0000-0001-8161-6138 Search for other works by this author on: Oxford Academic Google Scholar Dagmar Simon Dagmar Simon Department of Dermatology, Inselspital University Hospital of Bern, Bern, Switzerland https://orcid.org/0000-0001-8965-9407 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad453, https://doi.org/10.1093/bjd/ljad453 Published: 17 November 2023 Article history Editorial decision: 10 November 2023 Received: 10 November 2023 Accepted: 16 November 2023 Published: 17 November 2023
CD_99 G1 neutrophils modulate osteogenic differentiation of mesenchymal stem cells in the pathological process of ankylosing spondylitis
Authors: Xinzhe Feng, Chen Wang, Boyao Ji, Junjie Qiao, Yihong Xu, Shanbang Zhu, Zhou Ji, Bole Zhou, Wenwen Tong, Weidong Xu
Journal: Annals of the Rheumatic Diseases (2023)

This study aimed to identify the types and heterogeneity of cells within the spinal enthesis and investigate the underlying mechanisms of osteogenesis.
The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid insufficiency
Authors: Meng-Kai Ge, Cheng Zhang, Na Zhang, Ping He, Hai-Yan Cai, Song Li, Shuai Wu, Xi-Li Chu, Yu-Xue Zhang, Hong-Ming Ma, Li Xia, Shuo Yang, Jian-Xiu Yu, Shi-Ying Yao, Xiao-Long Zhou, Bing Su, Guo-Qiang Chen, Shao-Ming Shen
Journal: Cell Metabolism (2023)
Reorganization of adolescent prefrontal cortex circuitry is required for mouse cognitive maturation
Authors: Jastyn A. Pöpplau, Timo Schwarze, Mariia Dorofeikova, Irina Pochinok, Anne Günther, Annette Marquardt, Ileana L. Hanganu-Opatz
Journal: Neuron (2023)

Most cognitive functions involving the prefrontal cortex emerge during late development. Increasing evidence links this delayed maturation to the protracted timeline of prefrontal development, which likely does not reach full maturity before the end of adolescence. However, the underlying mechanisms that drive the emergence and fine-tuning of cognitive abilities during adolescence, caused by circuit wiring, are still unknown. Here, we continuously monitored prefrontal activity throughout the postnatal development of mice and showed that an initial activity increase was interrupted by an extensive microglia-mediated breakdown of activity, followed by the rewiring of circuit elements to achieve adult-like patterns and synchrony. Interfering with these processes during adolescence, but not adulthood, led to a long-lasting microglia-induced disruption of prefrontal activity and neuronal morphology and decreased cognitive abilities. These results identified a nonlinear reorganization of prefrontal circuits during adolescence and revealed its importance for adult network function and cognitive processing.
Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Chen He, Yi Li, Xi Jiang, Meng-Ni Jiang, Xian-Xian Zhao, Shu-Ren Ma, Dan Bao, Miao-Han Qiu, Jie Deng, Jin-Hai Wang, Peng Qu, Chun-Meng Jiang, Shao-Bin Jia, Shao-Qi Yang, Lei-Sheng Ru, Jia Feng, Wei Gao, Yong-Hui Huang, Ling Tao, Ying Han, Kan Yang, Xiao-Yan Wang, Wen-Juan Zhang, Bang-Mao Wang, Yue Li, You-Lin Yang, Jun-Xia Li, Jian-Qiu Sheng, Yi-Tong Ma, Min Cui, Si-Cong Ma, Xiao-Zeng Wang, Zhao-Shen Li, Zhuan Liao, Ya-Ling Han, Gregg W. Stone
Journal: JAMA Network Open (2023)

Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied.
Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents
Authors: Marcel Ballin, Martin Neovius, Francisco B. Ortega, Pontus Henriksson, Anna Nordström, Daniel Berglind, Peter Nordström, Viktor H. Ahlqvist
Journal: JAMA Network Open (2023)

Importance Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. Objective To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. Design, Setting, and Participants This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Exposures Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. Main Outcomes and Measures The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. Results A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%. Conclusions and Relevance In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.
Prevalence of Perinatal Anxiety and Related Disorders in Low- and Middle-Income Countries
Authors: Alexandra Roddy Mitchell, Hannah Gordon, Jessica Atkinson, Anthea Lindquist, Susan P. Walker, Anna Middleton, Stephen Tong, Roxanne Hastie
Journal: JAMA Network Open (2023)

Anxiety disorders are associated with poor maternal and neonatal outcomes. Women in low- and middle-income countries (LMICs) are thought to be disproportionally burdened by these disorders, yet their prevalence is unclear.
Educational Outcomes for Children at 7 to 9 Years of Age After Birth at 39 vs 40 to 42 Weeks’ Gestation
Authors: Richard J. Hiscock, Jessica A. Atkinson, Stephen Tong, Susan P. Walker, Amber Kennedy, Jeanie Y. L. Cheong, Jon L. Quach, Lyle C. Gurrin, Roxanne Hastie, Anthea Lindquist
Journal: JAMA Network Open (2023)

Importance Birth at 39 weeks’ gestation is common and thought to be safe for mother and neonate. However, findings of long-term outcomes for children born at this gestational age have been conflicting. Objective To evaluate the association of birth at 39 weeks’ gestation with childhood numeracy and literacy scores at ages 7 to 9 years compared with birth at 40 to 42 weeks’ gestation. Design, Setting, and Participants In this Australian statewide, population-based cohort study using a causal inference framework based on target trial emulation, perinatal data on births between January 1, 2005, and December 31, 2011, were linked to educational outcomes at 7 to 9 years of age. Statistical analyses were performed from December 2022 to June 2023. Exposure Birth at 39 weeks’ gestation compared with birth at 40 to 42 weeks’ gestation. Main Outcomes and Measures Numeracy and literacy outcomes were assessed at 7 to 9 years of age using Australian National Assessment Program–Literacy and Numeracy data and defined by overall z score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Multiple imputation and doubly robust inverse probability weighted regression adjustment were used to estimate population average causal effects. Results The study population included 155 575 children. Of these children, 49 456 (31.8%; 24 952 boys [50.5%]) were born at 39 weeks’ gestation and were compared with 106 119 (68.2%; 52 083 boys [49.1%]) born at 40 to 42 weeks’ gestation. Birth at 39 weeks’ gestation was not associated with altered educational outcomes for children aged 7 to 9 years compared with their peers born at 40 to 42 weeks’ gestation (mean [SE] z score, 0.0008 [0.0019] vs –0.0031 [0.0038]; adjusted risk difference, −0.004 [95% CI, −0.015 to 0.007]). Each educational domain was investigated, and no significant difference was found in grammar and punctuation (risk difference [RD], −0.006 [95% CI, −0.016 to 0.005]), numeracy (RD, −0.009 [95% CI, −0.020 to 0.001]), spelling (RD, 0.001 [95% CI, −0.011 to 0.0013]), reading (RD, −0.008 [95% CI, −0.019 to 0.003]), or writing (RD, 0.006 [95% CI, −0.005 to 0.016]) scores for children born at 39 weeks’ gestation compared with those born at 40 to 42 weeks’ gestation. Birth at 39 weeks’ gestation also did not increase the risk of scoring below national minimum standards in any of the 5 tested domains. Conclusions and Relevance Using data from a statewide linkage study to emulate the results of a target randomized clinical trial, this study suggests that there is no evidence of an association of birth at 39 weeks’ gestation with numeracy and literacy outcomes for children aged 7 to 9 years.
Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span
Authors: Adolf Pfefferbaum, Edith V. Sullivan, Kilian M. Pohl, Amanda Bischoff-Grethe, Susan A. Stoner, Eileen M. Moore, Edward P. Riley
Journal: JAMA Network Open (2023)

Importance Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. Objective To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants. Design, Setting, and Participants This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023. Main Outcomes and Measures Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable. Results Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum. Conclusions and Relevance The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.
Patient-Reported Outcomes, Tumor Markers, and Survival Outcomes in Advanced GI Cancer
Authors: Joy X. Jarnagin, Anurag Saraf, Islam Baiev, Gary Chi, Emily E. van Seventer, Amirkasra Mojtahed, Jill N. Allen, Jeffrey W. Clark, Lawrence Blaszkowsky, Bruce J. Giantonio, Colin D. Weekes, Samuel J. Klempner, Joseph W. Franses, Eric J. Roeland, Lipika Goyal, Giulia Siravegna, Nora Horick, Ryan B. Corcoran, Ryan D. Nipp, Aparna R. Parikh
Journal: JAMA Network Open (2023)

Patient-reported outcomes (PROs), such as quality of life (QOL) and symptoms, are often associated with clinical outcomes in patients with cancer. In practice, oncologists use serum tumor markers (TMs) (ie, carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA 19-9]) and imaging to monitor clinical outcomes in patients with gastrointestinal cancer.
Antenatal Corticosteroid Treatment During the Late-Preterm Period and Neonatal Outcomes for Twin Pregnancies
Authors: Jie Zhu, Ying Zhao, Ping An, Yunhe Zhao, Shuyue Li, Jizi Zhou, Huanqiang Zhao, Qiongjie Zhou, Xiaotian Li, Yu Xiong
Journal: JAMA Network Open (2023)

Importance Antenatal corticosteroid treatment of individuals with singletons at risk for delivery during the late-preterm period has been academically recommended. However, the evidence on the use of antenatal corticosteroid treatment for twins at risk for delivery during the late-preterm period is still lacking. Objective To evaluate whether antenatal corticosteroid treatment during the late-preterm period in twin pregnancies was associated with a lower risk of newborn morbidity. Design, Setting, and Participants This retrospective cohort study of twin pregnancies delivered from February 1, 2013, to September 30, 2020, in a university-affiliated hospital in China included 1974 individuals with twin pregnancies who were at risk for late preterm birth (34 weeks and 0 days to 36 weeks and 6 days of gestation). Data were analyzed from June 30 to July 13, 2023. Exposures Antenatal corticosteroid treatment during the late-preterm period. Main Outcomes and Measures The primary outcome measure was composite neonatal respiratory morbidity, defined as at least 1 of the following postnatal occurrences in at least 1 neonate of the twins: respiratory distress syndrome, mechanical ventilation, surfactant administration, transferred with respiratory complications, or neonatal death. Propensity score overlap weighting was used to analyze the association between antenatal corticosteroid treatment and the risk of neonatal outcomes. Results The study population consisted of 1974 individuals with twin pregnancies, including 303 (15.3%; mean [SD] maternal age, 30.8 [4.2] years) who received antenatal corticosteroid treatment and 1671 (84.7%; mean [SD] maternal age, 31.2 [4.0] years) who did not receive antenatal corticosteroid treatment. The propensity score overlap weighting showed no significant differences between the antenatal corticosteroid treatment group and the no–antenatal corticosteroid treatment group in the risk of neonatal primary outcome (29 of 303 [9.6%] vs 41 of 1671 [2.5%]; weighted odds ratio, 1.27 [95% CI, 0.60-2.76]). None of the subgroup interaction tests were significant for the neonatal primary outcome in terms of gestational age at delivery, year of delivery, chorionicity, at least 1 infant small for gestational age, intertwin growth discordance, and infant sex, and neither was the sensitivity analysis of using propensity score matching and a different administration-to-birth interval and treating twin infants as individuals. Conclusions and Relevance This cohort study found insufficient evidence that antenatal corticosteroid treatment during the late-preterm period in twin pregnancies could be associated with a lower risk of newborn morbidity. This new finding can provide a reference for clinical practice.